Effects of putative K+ channel activator BRL-34915 on arterial contraction and 86Rb efflux.
Segments of thoracic aorta, mesenteric and tail arteries from male Wistar rats were used for the determination of isometric relaxation responses to BRL-34915 [chromakalin or (+/-)-6-cyano-3,4-dihydro-2,2-dimethyl-trans-4-(2-oxo-1-pyrrolidyl )-2H-benzo- [b]-pyran-3-ol] after contraction with half-maximal (ED50) values of norepinephrine or high K(+)-physiological salt solution. Contiguous segments were incubated in the presence of 86Rb and used for study of the effects of BRL-34915 on 86Rb efflux. BRL-34915 produced a dose-dependent relaxation of norepinephrine- or K(+)-induced active stress that was essentially complete (100%) in the aorta and mesenteric artery but only partial (30-40%) in the tail artery. The ED50 value of BRL-34915 for relaxation responses was about 0.1 to 0.3 microM. BRL-34915 had no significant sustained effect on 86Rb efflux from the tail artery or mesenteric artery branches but produced a dose-dependent sustained increase in efflux from thoracic aorta and portal vein. Responses reached a peak effect in 2 to 4 min after exposure but subsequently declined over a slower time course. Efflux responses to BRL-34915 had peak values that averaged 100 to 150% above basal levels with an ED50 value of about 1 to 3 microM. This suggests a dissociation of the effects of BRL-34915 in relaxation and efflux experiments. Treatment with 30 microM BRL-34915 decreased both the initial and sustained components of the subsequent 86Rb efflux response to 10 microM norepinephrine in both thoracic aorta and tail artery.(ABSTRACT TRUNCATED AT 250 WORDS)
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Bockus Research Institute, Graduate Hospital, Philadelphia, Pennsylvania.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000493:pharmacokinetics*; D014661:Vasoconstriction / Q000187:drug effects*
D000959:Antihypertensive Agents; D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D012413:Rubidium; D011188:Potassium; D009638:Norepinephrine